# TRP Channels as Master Controllers of Lens Function

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2022 · $390,653

## Abstract

To function normally, all cells must maintain ion homeostasis and regulate water content.
The lens is unusual because it is made from a packed mass of fiber cells that are
incapable of independently maintaining ion and water homeostasis. The fiber cells rely
on ion transport mechanisms in a monolayer of epithelial cells at the lens surface. Na,K-
ATPase and NKCC1 activity are particularly important. To monitor and control this
arrangement, the lens has come to rely on exquisitely specialized remote control
mechanisms that utilize TRPV4 and TRPV1 channels. A TRPV4 feedback loop senses
swelling in the fiber mass and increases Na,K-ATPase activity to compensate. A TRPV1
feedback loop senses shrinkage in the fiber mass and increases NKCC1 activity to
compensate. The feedback loops are important. They explain homeostatic regulation of
lens ion transport as well as intracellular hydrostatic pressure, and they fit with the
Mathias model of lens circulation. TRPV4 and TRPV1 appear to be master controllers of
lens homeostasis. The specific aims are: (1) Test the hypothesis that the
TRPV4/hemichannel/Na,K-ATPase response to swelling stretch involves a functional link
between TRPV4 and the actin cytoskeleton; (2) Test the hypothesis that the
TRPV1/ERK/NKCC1 response to shrinkage involves a functional link between TRPV1
and the tubulin cytoskeleton; (3) Explore reserve mechanisms of lens ion and water
homeostasis. Aims 1 and 2 focus on unanswered mechanistic questions regarding
TRPV4 and TRPV1 activation by opposing mechanical stimuli, TRPV4-dependent
hemichannel opening, and the mechanism of NKCC1 activation. Aim 3 follows up pilot
studies on reserve mechanisms that support slower homeostatic responses or serve as a
fail-safe backup. The proposed studies are highly significant as regards human vision
because preservation of lens transparency and refractive index gradient depends on ion
and water homeostasis.

## Key facts

- **NIH application ID:** 10470896
- **Project number:** 5R01EY009532-29
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Nicholas A Delamere
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $390,653
- **Award type:** 5
- **Project period:** 1993-01-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10470896

## Citation

> US National Institutes of Health, RePORTER application 10470896, TRP Channels as Master Controllers of Lens Function (5R01EY009532-29). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10470896. Licensed CC0.

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